The proposed Center of Excellence for Malaria Research will focus on the epidemiology, vector biology and genetic diversity of malaria parasites under conditions typical of much of southern Africa. The research will be conducted in three endemic areas with different levels of malaria transmission and stages of control. The main research site will be located at the Malaria Institute at Macha (MIAM) in the Choma District of the Southern Province of Zambia. This is a semi-arid region that has a history of intense seasonal malaria transmission. While chemotherapy to reduce deaths from malaria has been in effect for over 20 years, no vector control interventions were implemented until 2007. The second field site will be at the Tropical Disease Research Centre (TDRC) in the Nchelenge District in the Luapula Province in northern Zambia, in the environs of Lake Mweru. This is a high transmission area with hyper- to holo-endemic malaria. The third field site will be at the Biomedical Research Training Institute (BRTI) in Mutasa District in Manicaland Province, Zimbabwe. This region was under an effective malaria control program for about 50 years but the program was terminated in the late 1990's. Consequently, there has been a resurgence of malaria. The ecological, geographical and demographic differences between these research areas provide a range of epidemiological conditions to investigate malaria transmission and control in southern Africa, specifically spatio-temporal patterns of transmission, vector biology and parasite diversity. Studies of malaria epidemiology will focus on hospital, clinic and community-based prospective studies to track spatial and temporal changes in transmission. Population genetic studies of the vector and parasite will allow characterization of the genetic heterogeneity associated with natural and imposed bottle necks and the changing frequency of insecticide resistance and antimalarial resistance mutations. The project Cores, consisting of Environmental Surveillance, Genomics and Data Management/Biostatistics provide links between the three research areas. An integrated relational data base will link information across space and time. The Training/Career Development Program will be coordinated at the University of Zambia and the Johns Hopkins School of Public Health and will take advantage of local capacity to strengthen their training programs to ensure the Center of Excellence for Malaria Research is sustained after the completion of this program.